Phospho-TGF-beta Receptor I (Ser165) (F5E2G) Rabbit Monoclonal Antibody recognizes endogenous levels of TGF-beta Receptor I protein only when phosphorylated at Ser165.

Mouse, Rat

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser165 of human TGF-β Receptor I protein.

Transforming growth factor-β (TGF-β) proteins belong to the TGF-β superfamily of cytokines that play a critical role in regulating cell proliferation and differentiation, developmental patterning and morphogenesis, and disease pathogenesis (1-3). TGF-β ligands elicit signaling through three cell surface receptors: type I (RI), type II (RII), and type III (RIII) TGF-β receptors. Type I and type II receptors are serine/threonine kinases that form a heteromeric complex following ligand binding to the type II receptor. In response to ligand binding, the type II receptors form a stable complex with the type I receptors, triggering phosphorylation and activation of the type I receptor (4). This results in the recruitment of receptor-mediated SMADs (SMAD2, SMAD3), which are phosphorylated by the type I kinase in an SSXS domain in the C-terminus. This leads to recruitment of the co-SMAD (SMAD4), and subsequent translocation of this heteromeric SMAD complex to the nucleus, where it regulates transcription of target genes (5-7). The type III receptor, also known as betaglycan, is a transmembrane proteoglycan with a large extracellular domain that binds TGF-β with high affinity but lacks a cytoplasmic signaling domain. Expression of the type III receptor can regulate TGF-β signaling through presentation of the ligand to the signaling complex (8).

Ligand banding and activation of type I receptor phosphorylates the protein at Ser165 and across a glycine, serine, threonine-rich domain (GS domain) at Thr185, Thr186, Ser187, Ser189, and Ser191 (9). Phosphorylation at Ser165 is not critical for transmission of TGF-β signals for transcription, cell growth, or migration, but is required for TGF-β-mediated extracellular matrix (ECM) formation and apoptotic signaling (9). Rottlerin, an activator of Ca2+-activated K+ channels, was shown to suppress TGF-β RI phosphorylation at Ser165 in in vitro and in vivo models of liver fibrosis, resulting in downregulation of pro-fibrotic TGF-β/Smad signaling (10). Overexpression of decorin, an ECM-protective protein, in hepatocullar carcinoma cells increased TGF-β RII expression and TGF-β RI phosphorylation at Ser165, suppressing the proliferation of these cells (11).